The basic hypothesis that will continue to be tested may be stated: is aging accompanied (or caused) by an accumulation of DNA damage in those non-dividing tissues which are not repopulated during the life- time of a mammal. The approaches will be; 1) The fate of rejoined DNA strand breaks in the retinas and cerebella of rabbits will be followed over extended periods of time after low doses of gamma-irradiation. The integrity of the repaired DNA structures in the photoreceptor cell complement of the retina will be studied in conjunction with physiological function, expressed as the electrical response (electroretinogram) of the retina, and possible histo(patho)logical changes. 2) Confirmation or denial of the provisional finding"....that there is a finite possibility the DNA structure in the internal granular-layer neurons of the beagle cerebellum decreases in molecular size with age." 3) To explore the integrity of the overall DNA structures in peripheral lymphocytes with age. 4) To study the ability of irradiated primary diploid fibroblasts to reconstitute their overall DNA structures as a function of senescence in culture. These proliferating cells will provide comparisons for their non-dividing counterparts. The first three of these studies are also of potential importance to radiotherapy, particularly the radiotherapy of the central nervous system. Strand breakage in neuronal DNA will be measured by the alkaline- EDTA reorienting zonal ultracentrifuge technique especially developed for the purpose in this laboratory during the present funding period. Electroretinograms and histo(patho)logical examinations will be made by standard methods.